[1]王圣杰,郑春松,朱晓勤,等.应用计算机模拟技术探讨人参和当归配伍延缓关节软骨退变的协同作用机制[J].中医正骨,2020,32(11):1-7.
　WANG Shengjie,ZHENG Chunsong,ZHU Xiaoqin,et al.A study of mechanisms of the synergistic effects of combination of ginseng and angelica sinensis in delaying articular cartilage degeneration by using computer simulation technology[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2020,32(11):1-7.
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应用计算机模拟技术探讨人参和当归配伍延缓关节软骨退变的协同作用机制()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第32卷
期数:
2020年11期
页码:
1-7
栏目:
基础研究
出版日期:
2020-11-20

文章信息/Info

Title:
A study of mechanisms of the synergistic effects of combination of ginseng and angelica sinensis in delaying articular cartilage degeneration by using computer simulation technology
作者:
王圣杰1; 郑春松2; 朱晓勤3; 付长龙2; 叶蕻芝2
(1.福建中医药大学药学院,福建 福州 350122; 2.福建中医药大学中西医结合研究院,福建 福州 350122; 3.福建省中西医结合老年性疾病重点实验室,福建 福州 350122)
Author(s):
WANG Shengjie1; ZHENG Chunsong2; ZHU Xiaoqin3; FU Changlong2; YE Hongzhi2
1.Pharmaceutical college of Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China2.Academy of Integrated Medicine affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China3.Fujian Key Laboratory of Integrated Medicine on Geriatrics,Fuzhou 350122,Fujian,China
关键词:
人参;  当归;  药对;  中药配伍;  骨关节炎;  软骨; 关节;  计算机模拟
Keywords:
ginseng;  angelica sinensis;  paired drugs;  compatibility(TCD);  osteoarthritis;  cartilage; articular;  computer simulation
摘要:
目的:探讨人参和当归配伍延缓关节软骨退变的协同作用机制。方法:①从北京大学天然产物库和中药系统药理学数据库及分析平台等数据库,检索出190个人参的化学成分和125个当归的化学成分,构建各自的化学成分数据集; 从化学结构角度进行聚类分析,并计算二者的全局指纹相似度。②依托定量构效关系及主成分分析平台,分析人参和当归化学成分数据集的化学空间。③以基质金属蛋白酶(matrix metalloproteinase,MMP)-1、MMP-3、MMP-13、聚蛋白多糖酶1(a disintegrin and metalloproteinase with thrombospondin motifs-4,ADAMTS-4)和聚蛋白多糖酶2(ADAMTS-5)为延缓关节软骨退变的靶点,利用分子对接和生物网络等平台,研究其与人参、当归中化学成分的相互作用,并构建人参和当归延缓关节软骨退变的化合物-靶点网络,分析人参和当归配伍延缓关节软骨退变的协同作用机制。结果:①对人参和当归化学成分数据集进行聚类,发现人参和当归化学成分数据集在第1、2、3、4、5、7、8、9、10类存在交集,但在第6类仅出现当归的化学成分; 对2个数据集的全局指纹进行比较,发现其相似度分值为0.621 8。②人参和当归化学成分数据集存在部分相同或相近的化学空间分布。③人参化合物-靶点网络显示人参具有40个延缓关节软骨退变的潜在化合物,其药效物质基础主要为挥发油类、生物碱类、黄酮类、脂肪酸类,核心作用靶点为MMP-1、ADAMTS-5、MMP-3、ADAMTS-4和MMP-13; 当归化合物-靶点网络显示当归具有10个延缓关节软骨退变的潜在化合物,其药效物质基础主要为挥发油类、生物碱类、磷脂类、脂肪酸类,核心作用靶点为ADAMTS-5、MMP-1和MMP-3。结论:人参与当归在化学结构特征及化学空间分布上具有很大程度的相似性,配伍后具有更广的化学空间分布、更多的潜在活性物质种类和数量,可通过作用于相同及不同靶点,在延缓关节软骨退变方面起到协同作用。
Abstract:
To explore the mechanisms of the synergistic effects of combination of ginseng and angelica sinensis in delaying articular cartilage degeneration.Methods:One hundred and ninety chemical components of ginseng and 125 chemical components of angelica sinensis were searched out from Peking University Natural Product Library and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)respectively to build corresponding chemical components datasets.The cluster analysis of the two Chinese drugs was performed according to their chemical structures,and the global fingerprint-based similarity between them were calculated.The chemical spaces of chemical components datasets of ginseng and angelica sinensis were analyzed relying on the quantitative structure-activity relationship and principal component analysis platform.Matrix metalloproteinase(MMP)-1,MMP-3,MMP-13,a disintegrin and metalloproteinase with thrombospondin motifs-4(ADAMTS-4)and ADAMTS-5 were taken as the targets for delaying articular cartilage degeneration.The interactions between chemical components of ginseng and angelica sinensis and these targets were researched and the compound-target network of the two drugs for delaying articular cartilage degeneration was built by using molecular docking and bio-network technology for analyzing the synergistic effects of combination of ginseng and angelica sinensis in delaying articular cartilage degeneration.Results:The cluster analysis on chemical components datasets of ginseng and angelica sinensis was performed,and the results showed that there were intersections in the 1st,2nd,3rd,4th,5th,7th,8th,9th and 10th category,while only the chemical compound of angelica sinensis was found in the 6th category.The global fingerprint was compared between the two datasets,and the results showed that the similarity score was 0.621 8.The chemical spatial distribution of the chemical components datasets of ginseng were partially identical or similar to that of angelica sinensis.The compound-target networks of ginseng and angelica sinensis showed that there were 40 and 10 potential compounds in ginseng and angelica sinensis respectively for delaying articular cartilage degeneration,and the main pharmacodynamic material basis were volatile oils,alkaloids,flavonoids and fatty acids in ginseng and volatile oils,alkaloids,phospholipids and fatty acids in angelica sinensis,and the core therapeutic targets were MMP-1,ADAMTS-5,MMP-3,ADAMTS-4 and MMP-13 for ginseng and ADAMTS-5,MMP-1 and MMP-3 for angelica sinensis.Conclusion:The ginseng has great similarities to the angelica sinensis in chemical structure characteristics and chemical spatial distributions.The combination of the two drugs has wider distribution in chemical space and more types and quantities of potential active substances,and the two drugs have synergistic effects in delaying articular cartilage degeneration through acting on the same and different targets.

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备注/Memo

备注/Memo:
基金项目:福建省自然科学基金项目(2019J01354)
通讯作者:叶蕻芝 E-mail:yelin0930@163.com
更新日期/Last Update: 2020-11-20